Mucoadhesive polymers are crucial in drug delivery, as their adhesion to mucosal surfaces directly affects bioavailability and therapeutic efficacy. Although macroscopic properties such as wettability and swelling influence retention, linking these effects to molecular mechanisms remains challenging [1,2].

In this study, HPMC, Kollidon, and Carbopol were examined under varying levels of pH to evaluate both macroscopic and molecular aspects of mucoadhesion. Polymer swelling and surface expansion were monitored in real-time using surface dissolution imaging, providing insights into hydration dynamics and deformation. Surface energy calculations using the OWRK model revealed differences in interfacial interactions that may govern adhesion.

At the molecular level, Langmuir–Blodgett trough experiments with model lipid and mucin layers simulated key mucosal components [3]. Polymers were introduced beneath these layers, and changes in surface pressure and layer organization were tracked to assess adsorption kinetics and dominant interactions, including hydrogen bonding and hydrophobic forces.

Results demonstrated a correlation between macroscopic retention and molecular interactions. Polymers with optimal wettability and surface energy showed the strongest binding, while layer reorganization suggested a mechanistic basis for retention. Variations between polymers and pH conditions indicate that both intrinsic material properties and environmental factors modulate mucoadhesive performance.

Integrating macroscopic and molecular analyses provides a comprehensive understanding of polymer–mucosal interactions. These findings offer a rational framework for designing mucoadhesive polymers in advanced drug delivery systems, with the potential to enhance therapeutic outcomes.

Acknowledgments: This research was funded by the Polish Ministry of Science and Higher Education, Poland (NCN MINIATURA 9 nr 2025/09/X/NZ1/00482).

References:[1] Jawadi, Z., Yang, C., Haidar, Z. S., Santa Maria, P. L., Massa, S. (2022). Bio-Inspired Muco-Adhesive Polymers for Drug Delivery Applications. Polymers, 14(24), 5459. [2] Subramanian, P. (2021). Mucoadhesive Delivery System: A Smart Way to Improve Bioavailability of Nutraceuticals. Foods, 10(6), 1362. [3] Alp, G., Aydogan, N. (2020). Lipid-based mucus penetrating nanoparticles and their biophysical interactions with pulmonary mucus layer. European Journal of Pharmaceutics and Biopharmaceutics, 149, 45–57.